PubMed Health⌕ Search

Biomedical subjects

M Wittmann

Publications and source records attributed to M Wittmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

Activated human T lymphocytes express a functional C3a receptor.

The C3a molecule is an anaphylatoxin of the C system with a wide spectrum of proinflammatory effects predominantly on cells of myeloid origin. In this study we investigated the expression of the high affinity receptor for C3a (C3aR) in human T lymphocytes using receptor-specific mAb. C3aR expression was detected in CD4(+) and CD8(+) blood- or skin-derived T cell clones (TCC) from birch pollen-sensitized patients with atopic dermatitis. No significant difference in C3aR expression in CD4(+) or CD8(+) TCCs could be observed. In contrast to C3a(desArg), C3a led to a transient calcium flux in TCCs expressing the C3aR, whereas C3aR-negative TCCs were unreactive. Circulating T cells from patients suffering from severe inflammatory skin diseases expressed the C3aR, whereas no expression of C3aR could be found in unstimulated T lymphocytes from patients with mild inflammatory skin diseases or from healthy individuals. Type I IFNs, which are potent stimulators of cellular immunity, were identified as up-regulators of C3aR expression in vitro in freshly isolated or cloned T lymphocytes. Moreover, C3aR(+) T cells were found at the sites of injection in IFN-beta-treated patients with multiple sclerosis. These data provide direct evidence for the expression of C3aR on activated human T lymphocytes; this may point to a biological function of C3a in T cell-dependent diseases.

Antibodies, Monoclonal↗
PubMed2000

fs-pulse synthesis using phase modulation by impulsively excited molecular vibrations

We report the temporal characteristics of laser radiation transmitted through impulsively excited SF6 and exhibiting sideband Raman lines. Even without special dispersion control we observed a sequence of compressed fs pulses following with the period of the excited A(1g) vibrational mode of SF6. The use of both negative and positive group velocity dispersion compensation for the temporal compression was found to be as appropriately efficient. The results prove our new concept of the ultrafast molecular phase modulator.

Journal Article↗
PubMed2000

Activation of group II metabotropic glutamate receptors inhibits synaptic excitation of the substantia Nigra pars reticulata.

Loss of nigrostriatal dopaminergic neurons in Parkinson's disease (PD) leads to increased activity of glutamatergic neurons in the subthalamic nucleus (STN). Recent studies reveal that the resultant increase in STN-induced excitation of basal ganglia output nuclei is responsible for the disabling motor impairment characteristic of PD. On the basis of this, it is possible that any manipulation that reduces activity at excitatory STN synapses onto basal ganglia output nuclei could be useful in the treatment of PD. We now report that group II metabotropic glutamate receptors (mGluRs) are presynaptically localized on STN terminals and that activation of these receptors inhibits excitatory transmission at STN synapses. In agreement with the hypothesis that this could provide a therapeutic benefit in PD, a selective agonist of group II mGluRs induces a dramatic reversal of catalepsy in a rat model of PD. These results raise the exciting possibility that selective agonists of group II mGluRs could provide an entirely new approach to the treatment of PD. These novel therapeutic agents would provide a noninvasive pharmacological treatment that does not involve the manipulation of dopaminergic systems, thus avoiding the problems associated with current therapies.

Animals↗
PubMed2000

From above threshold ionization to statistical electron emission: the laser pulse-duration dependence of C60 photoelectron spectra

The photoelectron spectra of C60 ionized using a 790 nm laser with pulse durations varying from 25 fs to 5 ps have been determined. For 25 fs pulses, in the absence of fragmentation, the ionization mechanism is direct multiphoton ionization with clear observation of above threshold ionization. As the pulse duration is increased, this becomes dominated by a statistical ionization due to equilibration among the electronic degrees of freedom. For pulse durations on the order of a ps coupling to the vibrational degrees of freedom occurs and the well-known phenomenon of delayed (&mgr;s) ionization is observed.

Journal Article↗
PubMed2000

Momentum distributions of ne(n+) ions created by an intense ultrashort laser pulse

Vector momentum distributions of Ne(n+) (n = 1,2,3) ions created by 30 fs, approximately 1 PW/cm(2) laser pulses at 795 nm have been measured using recoil-ion momentum spectroscopy. Distinct maxima along the light polarization axis are observed at 4.0 and 7.5 a.u. for Ne2+ and Ne3+ production, respectively. Hence, mechanisms based on an instantaneous release of two (or more) electrons can be ruled out as a dominant contribution to nonsequential strong-field multiple ionization. The positions of the maxima are in accord with kinematical constraints set by the classical "rescattering model."

Journal Article↗
PubMed2000

Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson's disease and related disorders.

The basal ganglia (BG) are a set of interconnected subcortical structures that play a critical role in motor control. The BG are thought to control movements by a delicate balance of transmission through two BG circuits that connect the input and output nuclei: the direct and the indirect pathways. The BG are also involved in a number of movement disorders. Most notably, the primary pathophysiological change that gives rise to the motor symptoms of Parkinson's Disease (PD) is the loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) that are involved in modulating function of the striatum and other BG structures. This ultimately results in an increase in activity of the indirect pathway relative to the direct pathway and the hallmark PD symptoms of rigidity, bradykinesia, and akinesia. A great deal of effort has been dedicated to finding treatments for this disease. The current pharmacotherapies are aimed at replacing the missing dopamine, while the current surgical treatments are aimed at reducing transmission through the indirect pathway. Dopamine replacement therapy has proven to be helpful, but is associated with severe side effects that limit treatment and a loss of efficacy with progression of the disease. Recently developed surgical therapies have been highly effective, but are highly invasive, expensive, and assessable to a small minority of patients. For these reasons, new effort has been dedicated to finding pharmacological treatment options that will be effective in reducing transmission through the indirect pathway. Members of the metabotropic glutamate receptor (mGluR) family have emerged as interesting and promising targets for such a treatment. This review will explore the most recent advances in the understanding of mGluR localization and function in the BG motor circuit and the implications of those findings for the potential therapeutic role of mGluR-targeted compounds for PD.

Basal Ganglia↗
PubMed2000

Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB).

BACKGROUND: Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30-60% of S. aureus strains isolated from patients with AD are able to produce exotoxins with superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA-D) and toxic shock syndrome toxin-1 (TSST-1). Recently, it was demonstrated that the presence of IgE antibodies to SEA and SEB is correlated with the severity of skin lesions in children with AD. To determine the relevance of staphylococcal enterotoxins in adult patients with AD, we investigated the relationship between the severity of skin lesions and sensitization to SEA and SEB. METHODS: Clinical severity was determined by the SCORAD index. Circulating IgE antibodies to SEA and SEB, serum eosinophil cationic protein (ECP) levels, and urine eosinophil protein X (EPX) levels were measured. RESULTS: The skin condition was significantly worse in patients sensitized to SEB than in unsensitized patients. Serum ECP and urine EPX levels were found to be significantly higher in SEB-sensitized patients, confirming the higher degree of cutaneous inflammation. CONCLUSIONS: Our results demonstrate a relationship between severity of skin lesions and sensitization to SEB in adult patients with AD, but a relationship between disease activity and sensitization to SEA could not be shown.

Adolescent↗
PubMed2000

Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury.

BACKGROUND: We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (MPhi) infiltration. METHODS: Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial MPhis were counted. RESULTS: In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant MPhi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, MPhis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize blood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial MPhi infiltration significantly. CONCLUSION: MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to MPhi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.

Angiotensin Receptor Antagonists↗
PubMed2000

[Methods for the costing process in the field of economic evaluation of a rehabilitation program for patients with chronic obstructive lung diseases].

Studies in health economics especially economic evaluations of health care technologies and programmes are getting more and more important. However, in Germany there are no established, validated and commonly used instruments for the costing process. For the economic evaluation of a rehabilitation programme for patients with chronic lung diseases such as asthma and chronic bronchitis we developed methods for identification, measurement and validation of resource use during the inpatient rehabilitation programme and during the outpatient follow-up period. These methods are based on methodological considerations as well as on practical experience from conducting a pilot study. With regard to the inpatient setting all relevant diagnostic and therapeutic resource uses could be measured basing on routine clinical documentation and validated by using the cost accounting of the clinic. For measuring the use of resources during the follow-up period in an outpatient setting no reliable administrative data are accessible. Hence, we compared a standardised retrospective patient questionnaire used in a 20-minute interview (n = 50) and a cost diary for the continuing documentation by the patient over a period of 4 weeks (n = 50). Both tools were useful for measuring all relevant resource uses in sufficient detail, but because of higher participation rates and lower dropouts the structured interview appears to be more suitable. Average total costs per month were 1591 DM (interview), respectively 1867 DM (cost diary). Besides productivity loss, costs for medication and GP visits caused the relatively highest resource uses. Practicable instruments were developed for the costing process as part of an economic evaluation in a German rehabilitation setting for pulmonary diseases. After individual modification, these could also be used for different indications and in other institutional settings.

Adolescent↗
PubMed2000

Efferent and afferent innervation of primate trabecular meshwork and scleral spur.

PURPOSE: To determine the correlation between nerve terminals and cells or extracellular matrix (ECM) components in different portions of the primate trabecular meshwork (TM) and scleral spur (SS). METHODS: Serial sagittal and tangential sections through the anterior segments of 10 cynomolgus monkey eyes and 12 human eyes were investigated immunohistochemically with antibodies against the vesicular acetylcholine transporter (VACHT), vasoactive intestinal polypeptide (VIP), tyrosine-hydroxylase (TH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), and galanin (GAL) and with a reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reaction. The distribution of the terminals was compared with that of alpha-smooth-muscle actin (SMA) staining in TM and SS. The relationship between terminals and adjacent cells or ECM components was also studied in ultrathin sections through the TM and SS of 11 monkey eyes cut in sagittal, tangential, and frontal planes. RESULTS: NADPHd-positive nerve terminals were present, especially in the outer portion of both human and monkey TM and in the SS. VACHT-immunoreactive (IR) fibers were found in human but not in monkey SS and TM. The fibers were most numerous in the elongated SS and posterior TM where most cells also stained for SMA. SP- and CGRP-IR nerve endings were also more numerous in the outer TM and SS than in the inner TM. Ultrastructurally, staining for SP was seen in nerve endings containing mitochondria and dense core vesicles and was in contact with the cribriform elastic network. In the posterior SS of monkey eyes were large terminals similar to those previously described in human eyes. CONCLUSIONS: The results show for the first time that in the primate TM and SS, there are cholinergic and nitrergic nerve terminals that could induce contraction and relaxation of TM and SS cells. Terminals in contact with the elastic-like network of the TM and containing SP-IR resemble afferent mechanoreceptor-like terminals in other parts of the body. These findings raise the possibility that the TM may have some ability to self-regulate aqueous humor outflow.

Actins↗
PubMed1999

Suppression of interleukin-12 production by human monocytes after preincubation with lipopolysaccharide.

Interleukin-12 (IL-12) is a potent proinflammatory and immunoregulatory cytokine skewing T lymphocytes to express a type 1 cytokine pattern. Optimal expression of IL-12 mRNA and bioactivity in vitro requires specific priming of monocytes by interferon-gamma (IFN-gamma) or granulocyte-macrophage colony-stimulating factor (GM-CSF) before lipopolysaccharide (LPS) stimulation. We show here for the first time that the production of IL-12 by IFN-gamma- or GM-CSF-primed human monocytes can be completely suppressed by preincubation with LPS (from Escherichia coli Serotype 055:B5) for 6 to 24 hours before the priming procedure. A dose-dependent suppression of IL-12p70 was measured on the levels of intracellular cytokine production and cytokine secretion. mRNA studies on the expression of p40 and p35 showed an LPS-induced downregulation of both subunits. The results of several different experimental approaches suggest that IL-12 downregulation was not due to endogenous IL-10, IL-4, prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), or nitric oxide (NO) production induced by LPS. Moreover, preincubation of monocytes with LPS did not lead to a downregulation of the CD14 antigen, which is an LPS receptor. LPS preincubation in this experimental setting did not result in a general hyporesponsiveness of the monocytes, as IL-6 production as well as IFN-gamma-induced upregulation of CD54 did not decline. Downregulation of IL-12 was not due to changes in mRNA stability. These findings show that the immunoregulatory important cytokine, IL-12, underlies itself a complex regulation.

Antiviral Agents↗
PubMed1999

C5a suppresses the production of IL-12 by IFN-gamma-primed and lipopolysaccharide-challenged human monocytes.

IL-12 is a key mediator of the immune response, skewing T lymphocytes toward a type 1 cytokine pattern. Priming with IFN-gamma or GM-CSF is required for expression of IL-12p70 by cells in which IL-12 is inducible by bacterial products such as LPS. We here show for the first time that the production of bioactive IL-12 by human monocytes can be significantly suppressed by C5a if applied to IFN-gamma-primed monocytes before LPS stimulation. There was a dose-dependent suppression by IL-12 (p70) on the levels of intracellular cytokine production and cytokine secretion. mRNA studies consistently showed a reduction of IL-12p40 and IL-12p35 expression by stimulation in the presence of C5a. The results of several different experimental approaches suggest that IL-12 down-regulation was not due to endogenous IL-10, IL-4, or PGE2 production induced by C5a. Moreover, stimulation of IFN-gamma-primed monocytes with C5a did not lead to a down-regulation of the CD14 Ag, which is an LPS receptor. These findings show that the anaphylatoxin C5a has the capacity to directly interact with the complex regulation of IL-12.

Adjuvants, Immunologic↗
PubMed1999

Sodium channels (from rat, mouse, and man) in neuroblastoma cells and different expression systems have similar sensitivities to pentobarbital.

Current understanding of the molecular mechanisms of anaesthesia entails multiple molecular sites of anaesthetic action, each more or less important for a specific anaesthetic drug used. For some molecular anaesthetic targets such as the GABA(A), and acetylcholine receptors as well as potassium channels, large differences in anaesthetic effects and sensitivity between different receptor subtypes have been found. Voltage-gated sodium channels have been shown to be affected at clinical concentrations of pentobarbital. However, these results were obtained in an expression system, and anaesthetic sensitivity may be dependent on sodium channel subtype and subunit composition, too. Therefore, we compared the sensitivity of voltage-gated sodium channels to pentobarbital in human (SHSYSY) and mouse (N1 E-115) neuroblastoma cell lines as well as an HEK293-cell expression system with previously reported data with other sodium channel subtypes. Remarkably, for all sodium channel subtypes studied as well as all subtypes reported in the literature, pentobarbital had qualitatively identical effects with some quantitative differences, and at potentials near the action potential threshold sodium currents were significantly reduced by clinical concentrations of pentobarbital.

Action Potentials↗
PubMed1999

Auditory temporal-order judgement is impaired in patients with cortical lesions in posterior regions of the left hemisphere.

Auditory temporal-order judgement was investigated in patients suffering from unilateral focal brain lesions, localized in anterior or posterior regions of the left hemisphere (LH) (resulting in non-fluent or fluent aphasia, respectively), or in predominantly subcortical regions of this hemisphere (without aphasic syndromes) and in anterior or posterior regions of the right hemisphere. The temporal order threshold was measured as the minimum time interval between two clicks presented consecutively and binaurally via headphones (one to each ear) that was necessary for a subject to indicate the temporal order of the two stimuli. Only the patient group with fluent aphasia showed a significantly increased mean temporal-order threshold as compared to the controls. Our results indicate that fine temporal resolution for auditory stimuli is predominantly associated with posterior regions of the LH.

Aphasia↗
PubMed1999

Daily rhythm of temporal resolution in the auditory system.

Over a period of 24 hours, fusion thresholds (click durations 100 micros) were assessed in 7 subjects. Over the same period, order thresholds (click duration of 1 ms) were measured in 10 subjects (12 independent sessions). Auditory fusion thresholds showed a diurnal rhythm with a maximum performance (shortest intervals) around midnight. In contrast, order thresholds appear to be independent on the time of day. Sex specific differences in threshold levels were only observed in order thresholds but not in fusion thresholds.

Acoustics↗
PubMed1999

Birch pollen-related foods trigger atopic dermatitis in patients with specific cutaneous T-cell responses to birch pollen antigens.

BACKGROUND: Patients with inhalant allergy caused by birch pollen frequently demonstrate immediate symptoms to cross-reactive fruits, vegetables, or both. The nature of late eczematous reactions to pollen related food antigens has not been investigated in detail. OBJECTIVE: The purpose of this study was to find out whether isolated late eczematous reactions to birch pollen-related food antigens can be observed in patients with atopic dermatitis (AD) who are highly sensitized to birch pollen antigens. A possible linkage of such reactions with specific T-cell responses to birch pollen antigens in the blood and lesional skin was examined as well. METHODS: We examined 37 adult patients with AD and hypersensitivity to birch pollen but without any history of immediate responses to food challenges. These patients underwent an elimination diet, including all birch pollen-related food antigens, followed by a double-blind, placebo-controlled, oral provocation. Blood and skin biopsy specimens were taken to examine a birch pollen-specific lymphocyte response. RESULTS: Seventeen patients reacted with a deterioration of AD symptoms. Food- or birch pollen-specific IgE did not differentiate these patients from nonreactive patients. A significantly higher increase in the proportion of blood lymphocytes expressing the cutaneous lymphocyte antigen on incubation with birch pollen antigens was found in cells from reactive compared with nonreactive patients. The proliferative response of skin-derived T-cell lines from reactive patients to birch pollen extract or Bet v 1 was significantly higher than that of nonreactive patients. An enrichment of more than 25% of T-lymphocyte subpopulations defined by T-cell receptor-Vbeta elements was detected in the majority of such antigen-stimulated T-cell lines from responsive patients. A higher frequency of birch pollen-reactive T cells was calculated from limiting-dilution assays, and a higher rate of birch pollen-specific T-cell clones was generated from cultures with skin-derived T cells from reactive patients. CONCLUSION: Our results show, for the first time, that a subpopulation of patients with hypersensitivity to birch pollen and AD reacts with worsening of eczema after oral challenge with birch pollen-related foods and that a birch pollen-specific T-cell response can be found in the lesional skin of these patients.

Administration, Oral↗